Regulatory Misalignment: A Comparative Analysis of FDA Accelerated Approvals and Their Implications for the Brazilian Health System

Abstract

The Accelerated Approval (AA) pathway of the U.S. Food and Drug Administration (FDA) allows early access to therapies intended to address life-threatening conditions or diseases with no available therapeutic alternatives. Based on early-phase studies or surrogate endpoints, this accelerated pathway carries a considerable risk of failure, with 12.8% of indications (43 out of 336) eventually withdrawn after confirmatory clinical trials failed to demonstrate clinical benefit.

This study aimed to identify and quantify the regulatory misalignment associated with these withdrawals within Brazil’s tripartite health system (ANVISA, CONITEC, and ANS). Using a comparative cross-sectional analysis of public databases, we tracked the regulatory and reimbursement status of the 43 indications withdrawn by the FDA between 1996 and 2024.

The results reveal a systemic misalignment: nine (20.9%) of these indications remain actively approved in ANVISA’s drug labels. Furthermore, eight of these nine indications continue to be included in the ANS mandatory coverage list (Rol de Procedimentos) for the supplementary health system, and one indication (gefitinib) received a favorable incorporation recommendation by CONITEC for the Brazilian Unified Health System (SUS) more than one year after its withdrawal by the FDA.

This discrepancy exposes Brazilian patients to potentially ineffective therapies and generates significant allocative inefficiencies in both the public and private healthcare sectors. We conclude that Brazil must transition from a passive regulatory model to a proactive post-marketing surveillance system, with an integrated reassessment mechanism among ANVISA, CONITEC, and ANS.